Hydroformylation reactions

ABSTRACT

In a process for the hydroformylation of alkanes, alkenes or trialkylboranes under supercritical or near-critical conditions, hydroformylation is effected using a heterogeneous catalyst in a continuous flow reactor containing a supercritical or near-critical reaction medium. Selectivity of product formation may be achieved by independently varying one of more of the temperature, pressure, catalyst, mole ratios of hydrogen and carbon monoxide and flow rate.

This Application is a 371 of PCT/GB99/02058 filed Jun. 30, 1999.

The present invention relates to a method for carrying outhydroformylation reactions. Specifically the present invention relatesto the hydroformylation reactions catalysed by heterogeneous catalystsin near-critical or supercritical fluids.

BACKGROUND

The use of carbon monoxide as a reagent for organic synthesis is diversewith a wide number of reactions carried out. One process of industrialimportance is hydroformylation (also known as the “oxo process”) whichis used for large-scale production of aliphatic aldehydes and alcoholsfrom olefins (alkenes) using cobalt- or rhodium-based homogeneouscatalysts.

In general, the hydroformylation reaction involves reaction of an alkeneor alkyne with a mixture of carbon monoxide and hydrogen over a catalystat high pressure to produce a carbonyl compound. Mixtures of hydrogenand carbon monoxide are frequently referred to as synthesis gas or syngas.

FIG. 1 shows the hydroformylation of an alkene in general terms. Theresulting carbonyl compound, which may be the normal (n) or iso product,can then be reduced to give the corresponding alcohol. An alternativeroute is first to convert the alkene or alkyne to a trialkylborane andthen to react this product with carbon monoxide and a reducing agent.

It is well known that reactions of this type are limited by thesolubility of the gases in the liquid reagent or solvent (known as MassTransport Limitations). The use of supercritical fluids in thereplacement of conventional solvents for environmental reasons isgradually being adopted. The use of supercritical fluids as reactionmedia also gives higher solubilities of gases in the system and giveseffectively a higher activity of these reagents by overcoming MassTransport limitations.

Work has previously been carried out on batch systems using homogeneouscatalysts in supercritical fluids. The following are examples of knownheterogeneous hydroformylation reactions:

1) the Hydroformylation of olefins, Chemtracts: Org. Chem. 1996, 9 (6),318-321 and Chemtracts: Inorg. Chem. (1995), 7(2), 120-123.

2) The Hydroformylation of Propylene in a batch system using homogeneouscatalysis in Supercritical fluids is reported by Akgerman et al (FourthItalian Conference on Supercritical Fluids and their Applications,September 1997 Proceeding, page 263-269).

3) U.S. Pat. No. 5,198,589 describes a batch or continuous batch processusing homogenous catalysis.

However, the use of homogeneous catalysts and batch processes lead tothe problems of catalyst separation, long residence time and scale-uphazards. Indeed, it is quite a significant problem with the processesdescribed in these publications that the use of homogeneous catalystsrequires a separation step at the end of the process to recover thecatalysts, because this necessitates extra processing steps and thusincreases costs. Also, separation is particularly difficult in the caseof alkenes which have a chain length longer than C7 because separatingthe catalysts from the products by distillation requires hightemperatures which destroy the catalysts. Consequently, these processesinvolving alkenes having a chain length greater than C7 cannot becarried out in continuous-flow reactors (tubular reactors).

The use of homogeneous catalysts also means that these processes areusually carried out in batch or semi-batch reactors. Such conditionsrequire extensive capital expenditure when scaling up owing to thedesign requirement for vessels capable of working at high pressure. Theuse of batch systems also has the disadvantage of increased down timefor charging and discharging the reaction vessel. There is also theproblem that the product of the reaction may be a mixture ofthermodynamic and kinetic products, owing to the large residence time ofthe reactants in the reactor.

Work has been carried out in the past on heterogeneous catalysis forhydroformylations under conventional (i.e. not near-critical orsupercritical conditions). However, these reactions have never provedsuccessful, usually because of low conversion to the products andcatalyst deactivation. Heterogeneous catalysed hydroformylationreactions carried out in supercritical media have not previously beenreported. As a result, hydroformylation reactions cannot presently becarried out using a heterogenous catalyst on an industrial scale.

There is thus a need for a hydroformylation process in which thecatalyst can be easily separated from the product by simple filtration.Ideally, the process should enable separation to be achieved even forhydroformylations of alkenes, alkynes or trialkylboranes having chainlengths greater than C7.

There is also a requirement for a hydroformylation process in which acontinuous flow reactor (tubular reactor) can be used. Ideally, theprocess should allow the operator the ability to control residence timeas well as the other reaction parameters independently in order to allowgreater control of the reaction. There is also a need for a processwhich is more efficient and/or more selective than conventionalprocesses.

Surprisingly, we have found that hydroformylation of alkenes, alkynesand trialkylboranes can be effected using a heterogenous catalyst insupercritical media. Thus, by using a combination of a supercriticalmedium, comprising one or more components, and a heterogeneous catalyst(e.g. the Deloxan HK1 2% rhodium complex catalyst from Degussa) it ispossible to carry out hydroformylation reactions with high conversion.It is also possible to perform the reaction with good selectivity forthe n or iso products where there is the possibility of forming both thenormal and iso products. The present invention thus solves the problemsof the prior art by effecting the hydroformylation reaction underconditions close to or above the supercritical point of the reactionmedium in the presence of a heterogeneous catalyst in a continuous flowreactor.

According to the present invention, there is provided a process forhydroformylation of a substrate, wherein the substrate is selected fromalkenes, alkynes, and trialkylboranes and is reacted with hydrogen andcarbon monoxide in the presence of a heterogeneous catalyst, thesubstrate being a fluid in its supercritical or near-critical stateand/or, reaction taking place in the presence of a solvent for thesubstrate, the solvent being in its supercritical or rear-criticalstate, and the process being carried out in a continuous flow reactor.The yield and/or selectivity of the reaction may be influenced bycontrolling one or more of the reaction conditions of temperature,pressure, residence time, flow rate and catalyst.

In an embodiment, the catalyst comprises a support selected from: anorganosiloxane-polycondensate, an organosiloxane-copolycondensate, orpolymeric secondary and/or tertiary organosiloxanamine combinations; anda metal or metal complex in which the metal is selected from: platinum,nickel, palladium, cobalt, rhodium, iridium, iron, ruthenium, andosmium, and the catalyst optionally includes a promoter. Rhodium is aparticularly preferred metal.

Suitable catalysts thus include Deloxan HK1 which is a 2% Rh catalyst ona polyaminosiloxane support obtainable from Degussa.

The hydroformylation reaction of the present invention satisfies theabove requirements by providing a process in which the products can beseparated from the catalyst after reaction without difficulty. This istrue for reactions on alkenes, alkynes or trialkylboranes having a chainlength greater than C7. Hence alkenes, alkynes or trialkylboranes havinga chain length greater than C7 can be hydroformylated and the productseasily separated from the catalyst without the need for distillation orfurther work-up.

The process also results in yields and selectivities which are betterthan conventional processes. In particular, the feature of selectivityis an important feature of the invention because the iso product isfrequently a by-product of hydroformylation reactions carried out underconventional conditions in cases where the production of both normal andiso-compounds is possible. Thus, the process of the present inventioncan substantially reduce the incidence of the iso product if this isdesirable. In some circumstances the iso product may be the desiredproduct, in which case the reaction conditions may be optimised for theiso product.

The process of the present invention also enables the reaction to becarried out in a tubular reactor. The use of a tubular reactor has theadvantage of having a low inventory of reagents under high pressure atany moment hence increasing the overall safety of the process.

Furthermore, we have also found that under such conditions the reactorcan be made very efficient using only half the amount of syn gas whichis required by Akgerman et al. in the reported process. Surprisingly,alteration of the pressure in the reactor gives selectivity with regardto the ratio of n to iso products (this can be seen from Table 1 givenlater with Example 1). Thus, by varying the pressure of thesupercritical medium it is possible to achieve ratios greater than 3:1of the n:iso products.

In the process of the present invention at least one of the components,other than the hydrogen or carbon monoxide, is under supercritical ornear-critical conditions. One or more of temperature, pressure, flowrates, and hydrogen and carbon monoxide concentration may beindependently controlled for a given catalyst so as to influence theselectivity of the reaction. The catalyst may also be varied (either fora given set of conditions or under various conditions of temperature,pressure, flow rate etc.) to influence the yield and/or selectivity ofthe product.

The alkene, alkyne or trialkylborane substrate is hydroformylated in acontinuous process which preferably comprises the steps of:

(a) admixing a supply of an inert fluid as solvent with a supply of thesubstrate and a supply of hydrogen and carbon monoxide at pre-determinedflow rates;

(b) adjusting the temperature and pressure of the resulting admixture topre-determined values of temperature and pressure close to or above thecritical point of a fluid present in the reaction system and exclusiveof CO and H₂ to produce a reaction mixture from which the desiredcarbonyl product is formed as the major carbonyl product, wherein thechoice of the pre-determined values of temperature and pressure isdependent on which of the possible hydroformylation products is to beformed;

(c) exposing the reaction mixture to a heterogeneous catalyst tofacilitate reaction; and

(d) removing the reaction mixture after reaction from the region of thecatalyst and isolating the desired product by depressurisation of thereaction mixture.

The heterogeneous continuous flow system of the present invention offersa number of advantages compared with batch type systems or a homogenouscontinuous flow system. In particular, the present invention allows theformation of a desired end product in good yield and/or a selectivemanner by controlling one or more of: the temperature, the pressure ofthe reaction, by varying the catalyst used for a given set of reagents,the flow rate through the apparatus, and the mole ratios of the hydrogenand carbon monoxide to is the substrate.

The factors controlling the selectivity of hydroformylation will dependon the particular reaction and in some instances the temperature or thepressure will be the controlling factor, whereas in other cases thecatalyst or flow rate may be more important in determining the outcomeof the reaction. Suitable conditions for a given substrate and desiredproduct are thus determined in accordance with the present invention.

The present invention also offers the advantage that hazardous reagentsmay be used without the need for a high inventory of reagent at any onetime, since the organic compound and the hydrogen and carbon monoxideare continuously fed to the reactor.

Similarly, the reaction product or products are collected continuouslyfrom the reactor and do not therefore accumulate in large quantities inthe reactor. This has the further advantage that the products are lesslikely to suffer degradation. There is also a concomitant increase inthe safety of the process as compared to a batch-process when usinghazardous reagents or when forming hazardous products since thesematerials are not usually present in sufficient quantities to representa significant risk. Since the continuous flow process of the presentinvention also allows cleaner reactions to be performed than those of acorresponding batch-type process, the cost of purifying the products isreduced.

The present invention has the further advantage of providing higheryields and higher throughputs than conventional methods in some cases.Whilst the actual throughputs will inevitably depend on the particularreaction employed and the size of the apparatus, throughputs of 25 mlsper minute or higher are attainable using laboratory scale apparatus.Furthermore, selectivities in excess of 3 to 1 in favour of the normalcarbonyl product can easily be achieved using the process of the presentinvention.

The hydroformylation reaction of the present invention is performedclose to or above supercritical point of the desired medium. Any fluidhaving a supercritical point may be employed for the process of thepresent invention provided that it is compatible with the reactants. Inaddition, the alkene, alkyne or trialkylborane (if it is not a solid).may be both the substrate and the supercritical medium. However, inpractice the choice of fluid will depend upon the solubility of thesubstrate in the fluid since a function of the supercritical ornear-critical fluid is to act as a solvent for the substrate and thehydrogen and carbon monoxide. It is also important that the reactionmedium is inert with respect to the reactants and the products of thereaction in order to avoid undesirable side reactions. Particularlyfavoured media include carbon dioxide, sulphur dioxide, alkanes such asethane, propane and butane, and saturated halocarbons such astrichlorofluoromethane, dichlorofluoromethane, dichlorodifluoromethane,chlorotrifluoromethane, bromotrifluoromethane, trifluoromethane, andhexafluoroethane. The reaction medium may be a mixture of two or morefluids having critical points which do not require commerciallyunacceptable conditions of temperature and pressure in order to achievethe necessary conditions for reaction according to the presentinvention. For example, mixtures of carbon dioxide with an alkane suchas ethane or propane, or a mixture of carbon dioxide and sulphur dioxidemay be employed close to or above their theoretical critical points.

In the context of the present invention, the lower limit of theconditions suitable for supporting the hydroformylation reaction areconditions of temperature and pressure below but near the criticalpoint. When a fluid reaches its critical point its density issubstantially decreased relative to its density at its boiling point atnormal pressure. Small changes in pressure near the critical point causeadditional changes in density. The process will operate in the fluid attemperatures and pressures below the critical point but at which thedensity of the fluid is sufficient to ensure that the substrate and thehydrogen and carbon monoxide are substantially in a single phase. Theupper limit of temperature and pressure is governed by limitations ofthe apparatus.

Although aliphatic compounds are more difficult to hydroformylate thanaromatic compounds under the reaction conditions employed in the presentinvention, the hydroformylation of both aliphatic and aromatic compoundsis possible according to the present invention.

Product formation may be monitored in situ by means of IR spectrometryusing a suitably positioned high pressure IR cell, or by gaschromatography (GC) performed on samples withdrawn from the reactor.

The present invention will now be described by way of example only withreference to the Figures in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a hydroformylation reaction; and

FIG. 2 is a schematic diagram of a continuous flow reactor according tothe present invention.

The substrate 1, dissolved in an appropriate solvent if it is a solid,is pumped into mixer 2 which may include a stirrer 2 a where it is mixedwith fluid 3 which has been delivered from a reservoir via a pump tomixer 2. Mixing of substrate 1 and fluid 3 may equally be effectedwithout the use of a stirrer. Hydrogen and carbon monoxide in the formof mixture 4 is delivered from a reservoir via a compressor and a dosageunit (e.g. an injection valve) to mixer 2. The ratios of the hydrogenand carbon monoxide may be independently varied as required. Thehydrogen/carbon monoxide mixture 4 has a pressure of typically 200 to220 bar, inclusive. This pressure is obtained by means of conventionalpressure regulating apparatus. Addition of dissolved substrate 1 and/ormixture 4 may be continuous or may occur continuously in a step-wisemanner. The hydrogen/carbon monoxide mixture 4 is added via a switchingvalve or similar control means to give the required ratio of the mixture4 to the substrate 1. The ratio of hydrogen and carbon monoxide tosubstrate is chosen according to the reaction to be used and istypically in the range from 1.0:1.0, to 3.0:1.0, inclusive, equivalentsof syn gas (i.e. the mixture 4) per reaction.

The temperature and/or pressure of the mixture of substrate 1, fluid 3and the hydrogen/carbon monoxide mixture 4 is adjusted in mixer 2 to atemperature and pressure close to or above the critical point of fluid 3as required. Heating means or cooling means are provided in mixer 2 forthis purpose. The mixture is then passed into reactor 5 which contains acatalyst (not shown) fixed on a suitable support.

After an appropriate residence time in reactor 5 fluid 3, which containsthe product is passed into pressure reduction unit 6 and the products 7are removed via take a off tap after passing through pressure reductionunit 6. The flow rate of the reactants through reactor 5 is controlledby a valve (not shown) in pressure reducer 6. The quantity of materialsconsumed in the reaction and the rate of reaction are determined by thetemperature, the feed rate of substrate 1 into fluid 3 and the flow rateof fluid 3. Fluid 3, together with any unconsumed hydrogen and carbonmonoxide, is vented through a relief pipe 8 for subsequent recycling ordisposal.

The parameters of a typical reaction might involve a system pressure of60 to 140 bar (this will, of course, depend in part on the reactionmedia), a flow rate of the substrate of 0.5 to 20.0 ml/min, a reactortemperature of 40 to 360° C. (again, this will depend in part on thereaction media) and a flow rate of the supercritical or near criticalfluid of 0.65 to 1.65 l/min; however, these parameters do not implylimitations to within the respective ranges.

EXAMPLE 1

Oct-1-ene is pumped at 0.5 ml/min into a heated mixer which may includea stirrer where it is mixed with synthesis gas (syn gas). Thesupercritical reaction medium.is carbon dioxide and the system pressureis set via a pressure regulator on the carbon dioxide inlet. The reactoris set at the appropriate temperature (see Table 1) and the mixture ispassed through the reactor containing the heterogeneous catalyst(Deloxan HK1, ex Degussa). After reaction, the pressure is dropped via atwo-stage expansion valve through which the gaseous carbon dioxide isvented and the products are collected. The results obtained in thisreaction under various conditions are shown in Table 1, with analysis ofthe products being carried out by GC using normalised areas.

It is apparent from Table 1 that for a given reaction medium, variationof the temperature and ratio of substrate to hydrogen and carbonmonoxide (syn gas) allows control of the ratio of normal to iso carbonylproduct.

TABLE 1 Yield of Molar Aldehydes/ Flowrate Reactor Pressure EquivalentsReactor Conversion/ % n:iso of Temp/° C. Bar of Syn gas Volume/ml %(Nonanal) Ratio CO₂/(1/min) 150 100 1.5 5 89.6 55.6 2.4:1 0.65 150 1201.1 5 73.7 41.3 1.7:1 0.65 150 120 1.5 5 94.5 64.7 2.9:1 0.65 150 1201.9 5 96.4 70.5 3.5:1 0.65 150 140 1.5 5 94.3 79.2 1.9:1 0.65 100 1203.0 10 93.0 78.0 1.7:1 0.65

What is claimed is:
 1. A process for the continuous hydroformylation ofa substrate, wherein the substrate is selected from alkenes, alkynes,and trialkylboranes and is reacted with hydrogen and carbon monoxide inthe presence of a heterogeneous catalyst, the substrate being a fluid inits supercritical or near-critical state and/or, the reaction takingplace in the presence of a solvent for the substrate, the solvent beingin its supercritical or near-critical state, and the process beingcarried out in a continuous flow reactor.
 2. A process according toclaim 1, which comprises controlling one or more of the reactionconditions of temperature, pressure, residence time, flow rate andcatalyst so as to influence the yield and/or selectivity of thereaction.
 3. A process according to claim 1 or 2, wherein a solvent ispresent which is one or more of: carbon dioxide, an alkane, ammonia,nitrogen and a saturated halocarbon.
 4. A process according to claim 1,2 or 3, wherein the catalyst is a supported metal catalyst.
 5. A processaccording to claim 4, wherein the catalyst comprises: a support selectedfrom an organosiloxane-polycondensate, anorganosiloxane-co-polycondensate, and polymeric secondary and/ortertiary organosiloxanamine combinations; and a metal or metal complexin which the metal or metal portion of the metal complex is selectedfrom platinum, nickel, palladium, cobalt, rhodium, iridium, iron,ruthenium, and osmium.
 6. A process according to claim 5, wherein thecatalyst further comprises: a promoter.
 7. A process forhydroformylation of a substrate, wherein the substrate is selected fromalkenes, alkynes, and trialkylboranes and is reacted with hydrogen andcarbon monoxide in the presence of a heterogeneous catalyst and anadditional solvent being in a supercritical or near-critical state, andwherein one or more of the reaction conditions of temperature, pressure,residence time, flow rate and catalyst may be controlled so as toinfluence the yield and/or selectivity of the reaction.
 8. A processaccording to claim 7, wherein the process is carried out in a continuousflow reactor.
 9. A process according to claim 7, wherein the additionalsolvent is selected from carbon dioxide, an alkane, ammonia, nitrogen, asaturated halocarbon, the substrate and combinations thereof.
 10. Aprocess according to claim 7, wherein the catalyst is a supported metalcatalyst.
 11. A process according to claim 10, wherein the catalystcomprises: a support selected from an organosiloxane-polycondensate, anorganosiloxane-co-polycondensate, and polymeric secondary and/ortertiary organosiloxanamine combinations; and a metal or metal complexin which the metal or metal portion of the metal complex is selectedfrom platinum, nickel, palladium, cobalt, rhodium, iridium, iron,ruthenium and osmium.
 12. A process according to claim 11, wherein thecatalyst further comprises: a promoter.
 13. A process forhydroformylation of a substrate, wherein the substrate is selected fromalkenes, alkynes, and trialkylboranes, the substrate being a fluid in asupercritical or near-critical state, the process carried out in acontinuous flow reactor, the process comprising: reacting the substratewith hydrogen and carbon monoxide in the presence of a heterogeneouscatalyst.
 14. A process according to claim 13, further comprising:controlling one or more reaction conditions, the reaction conditionsincluding temperature, pressure, residence time, flow rate and thecatalyst, so as to influence the yield and/or selectivity of reaction.15. A process according to claim 14, wherein, in reacting, the catalystis a supported metal catalyst.
 16. A process according to claim 15,wherein, in reacting, the catalyst comprises: a support selected from anorganosiloxane-polycondensate, an organosiloxane-co-polycondensate, andpolymeric secondary and/or tertiary organosiloxanamine combinations; anda metal or metal complex in which the metal or metal portion of themetal complex is selected from platinum, nickel, palladium, cobalt,rhodium, iridium, iron, ruthenium and osmium.
 17. A process according toclaim 16, wherein, in reacting, the catalyst further comprises: apromoter.